The overall objective of the program is to study the neurohumoral control of the circulation in hypertension, heart failure, vascular disease, and myocardial ischemia. This supplemental request is to examine: 1. Basic mechanisms regulating the tone of vascular smooth muscle. 2. Certain aspects of the regulation of myocardial function in hypertrophy, ischemia and failure. These studies will include: a) an evaluation of mechanics and energetics of hypertrophied cardiac muscle; b) the synthesis and evaluation of a new analytical model of the left ventricle using deformation patterns and stress analysis; and c) the echocardiographic assessment of factors which determine the extent and severity of segmental myocardial dyskinesia after myocardial ischemia. 3. Mechanisms regulating the control of heart rate. 4. The changes in rate of biosynthesis of norepinephrine in hypertension and failure. 5. The changes in capillary permeability in heart failure. 6. The control of the renal microcirculation and its effect on renal function. 7. The effect of concomitant sympathectomy in aortoiliac reconstructive surgery using a quantitative assessment of limb blood flow in man. The program represents an interdisciplinary effort at intra and interdepartmental levels including both clinical and basic sciences departments. The support will provide resources to be shared by several investigators who have worked effectively together during the past 2 years and will provide an opportunity for additional new investigators with special expertise in new areas of investigation to extend the objectives of this program into in-depth examination of fundamental mechanisms as well as into areas of applied clinical research.